Periodontitis is a chronic disease of high prevalence in the United States and other countries. Successful treatment requires trained specialists and it is costly, sometimes painful, and not readily available to much of the population. There is a compelling need for new approaches to prevention and control. Recent developments support the idea that a vaccine may be feasible, especially in highly susceptible groups and individuals. Periodontitis is infectious, and identity of several specie of participating bacteria is known. Most patients mount a humoral immune response to antigens of the infecting pathogens. We do not know which antigens are involved, nor have we an understanding of the functional characteristics of the antibodies produced. Most importantly, we do not know if the antibodies are protective, destructive, or irrelevant to the course of the disease. This multidisciplinary program project proposes to resolve some of these fundamental issues. It consists of four separate but highly interrelated projects, and a core program that serves all projects. using ELISA tests, immunoblots, antibody- positive patient sera. and various fractions from relevant bacteria, we will identify and characterize the major antigens humans recognize. We will measure the quantity and biological activity of antibodies present in sera of patients and periodontally normal individuals. To determine whether serum antibodies are protective, destructive, or irrelevant to progression of periodontitis, we will induce humoral immunity in Macaca fascicularis, using a vaccine containing a newly developed adjuvant plus, killed B. gingivalis, and subsequently induce periodontitis in immunized and nonimmunized animals. We will monitor levels and properties of serum antibodies, and composition of the subgingival microflora. Presence and progress of the disease will be assessed by measurement of inflammation, attachment level, and alveolar bone loss. Successful completion of the studies will reveal which antigens are important, the functional characteristics of observed serum antibodies, the effect of immunization on composition of the subgingival microflora, and on initiation and progress of ligature-induced periodontitis.